Many physiological and anatomical changes of pregnancy affect the respiratory system. These changes often affect the presentation and management of the various respiratory illnesses in pregnancy. This article focuses on several important respiratory issues in pregnancy. The management of asthma, one of the most common chronic illnesses in pregnancy, remains largely unchanged compared to the nonpregnant state. Infectious respiratory illness, including pneumonia and tuberculosis, are similarly managed in pregnancy with antibiotics, although special attention may be needed for antibiotic choices with more pregnancy safety data. When mechanical ventilation is necessary, consideration should be given to the maternal hemodynamics of pregnancy and fetal oxygenation. Maintaining maternal oxygen saturation above 95% is recommended to sustain optimal fetal oxygenation. Cigarette smoking has known risks in pregnancy, and current practice guidelines recommend offering cognitive and pharmacologic interventions to pregnant women to assist in smoking cessation.
Highlights
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Asthma treatment is largely similar to the nonpregnant population and is safe for use in pregnancy.
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Shortness of breath is a common complaint in pregnancy, but in a tachypneic patient further investigation may be warranted.
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High-risk pregnant patients should be screened and treated for tuberculosis (TB).
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Nicotine replacement therapy is preferable to continued smoking in pregnancy.
Physiologic changes in the respiratory system with pregnancy
Pregnancy is associated with profound anatomical, physiological, and biochemical changes, which affect the different organ systems variably. Changes begin soon after fertilization and continue throughout gestation. Many of these adaptations occur in response to hormonal or mechanical stimuli, and they can either be misinterpreted as disease or mask a compromised status. For example, progesterone-mediated vasodilation can lead to increased mucosal vascularity and edema, presenting as rhinitis and causing an increased prevalence of epistaxis in pregnancy. On the other hand, because pregnancy is typically associated with lower levels of carbon dioxide (PaCO 2 ) than the normal nonpregnant state, a finding of “normal” PaCO 2 level in arterial blood gases may indicate impending respiratory failure, and this should prompt the clinician to consider intubation.
Mechanical changes to the respiratory system during pregnancy result from several adaptations the body undergoes to accommodate the growing uterus in the abdomen. Understandably, the diaphragm is elevated by about 4–5 cm past its original position . The clinical implication of this change is that a higher approach might be necessary while performing a thoracentesis on a pregnant woman. There is also an increase in the chest wall circumference and the anteroposterior diameter, resulting from hormone-induced relaxation of ligaments connecting the ribs to the sternum leading to an outward flare of the lower ribs. There is anecdotal experience to suggest that this leads to a mechanical stress on the lower ribs predisposing pregnant women to stress fractures from even minor trauma such as coughing .
Pregnancy has a major effect on lung volumes. It is associated with a 30–50% increase in tidal volume (TV), which occurs at the expense of the functional residual capacity (FRC) (FRC = residual volume (RV) + expiratory reserve volume (ERV)) . While the respiratory rate is not increased, minute ventilation (product of respiratory rate and TV) is increased, leading to a higher PaO 2 in the maternal circulation (104–108 mmHg or 13.8–14.3 kPa) and a reduction in PaCO 2 from 35-–40 mmHg (4.6–5.3 kPa) in the nonpregnant state to 27–32 mmHg (3.6–4.2 kPa) in pregnancy . Despite the changes in TV and FRC, spirometry remains unchanged in pregnancy. Therefore, abnormal spirometry results should be attributed to underlying respiratory illness and not to pregnancy itself .
The lower PaCO 2 in the maternal circulation results in a state of chronic respiratory alkalosis (pH 7.4–7.45), which is compensated for by an increase in renal excretion of bicarbonate, leading to a reduced serum bicarbonate level of 18–21 mmol/L . This has both advantages and disadvantages for the expectant mother. On the one hand, lower bicarbonate levels shift the hemoglobin oxygen dissociation curve to the right, so that the affinity of maternal hemoglobin to oxygen is reduced, thereby facilitating the transfer of oxygen to the fetus. On the other hand, this reduction in bicarbonate results in a lower buffering capacity, which makes the pregnant woman particularly susceptible to acidosis .
Approach to dyspnea in pregnancy
Shortness of breath is a common complaint in pregnancy, with over two-thirds of pregnant women experiencing some form of it during the gestation period. An increasing abdominal girth or weight gain alone are not enough to explain the symptoms as many women experience it in early gestation before such changes have occurred.
Dyspnea of pregnancy refers to a commonly encountered condition in pregnancy in which women describe a sense of “air hunger” or a “need to take a deep breath intermittently.” All too often, the patient will report that the shortness of breath was first noticed while conversing, because she cannot complete her sentence without pausing for a breath. Progesterone-induced stimulation of the respiratory center in the brain, necessary for the increase in TV with pregnancy, is thought to be the possible mechanism of this. By the third trimester, the majority of women will report some decrease in exercise tolerance most likely resulting from mechanical changes associated with weight gain and decreased venous return.
When a pregnant woman complains of dyspnea, distinguishing between underlying disease and normal pregnancy-related dyspnea can be a difficult diagnostic problem. While the differential diagnosis of dyspnea in general includes a myriad of conditions, the list of conditions of particular importance in pregnancy is relatively small. Table 1 describes these causes, clinical features characteristic for the condition, and a brief summary of possible investigations and interventions.
| Causes of dyspnea | Clinical characteristic | Helpful investigations | Interventions |
|---|---|---|---|
| Dyspnea of pregnancy | Need to take a deep breath intermittently, or inability to get a deep enough breath | None | Reassurance |
| Asthma/airways disease | Dyspnea with chest tightness or wheezing | Spirometry, pre- and post-bronchodilator | Inhaled beta agonists ± inhaled steroids |
| Cardiac disease | Myocardial/valvular dysfunction: progressive orthopnea or orthopnea with paroxysmal nocturnal dyspnea. Often present at end of second trimester or in early postpartum period when fluid shifts occur | Echocardiogram | Diuretics, beta-blockers as indicated. ACE inhibitors contraindicated in pregnancy |
| Arrhythmia | Sudden onset and cessation, associated sensation of palpitations or chest discomfort | Electrocardiogram, Holter or event monitor | Beta-blockers, calcium channel blockers |
| Venous thromboembolism | Sudden onset, any trimester. May have associated DVT features | Computerized tomography pulmonary angiogram, V/Q scan, lower-extremity Dopplers | Anticoagulation with injectable heparins in pregnancy, warfarin in the postpartum period. |
Approach to dyspnea in pregnancy
Shortness of breath is a common complaint in pregnancy, with over two-thirds of pregnant women experiencing some form of it during the gestation period. An increasing abdominal girth or weight gain alone are not enough to explain the symptoms as many women experience it in early gestation before such changes have occurred.
Dyspnea of pregnancy refers to a commonly encountered condition in pregnancy in which women describe a sense of “air hunger” or a “need to take a deep breath intermittently.” All too often, the patient will report that the shortness of breath was first noticed while conversing, because she cannot complete her sentence without pausing for a breath. Progesterone-induced stimulation of the respiratory center in the brain, necessary for the increase in TV with pregnancy, is thought to be the possible mechanism of this. By the third trimester, the majority of women will report some decrease in exercise tolerance most likely resulting from mechanical changes associated with weight gain and decreased venous return.
When a pregnant woman complains of dyspnea, distinguishing between underlying disease and normal pregnancy-related dyspnea can be a difficult diagnostic problem. While the differential diagnosis of dyspnea in general includes a myriad of conditions, the list of conditions of particular importance in pregnancy is relatively small. Table 1 describes these causes, clinical features characteristic for the condition, and a brief summary of possible investigations and interventions.
| Causes of dyspnea | Clinical characteristic | Helpful investigations | Interventions |
|---|---|---|---|
| Dyspnea of pregnancy | Need to take a deep breath intermittently, or inability to get a deep enough breath | None | Reassurance |
| Asthma/airways disease | Dyspnea with chest tightness or wheezing | Spirometry, pre- and post-bronchodilator | Inhaled beta agonists ± inhaled steroids |
| Cardiac disease | Myocardial/valvular dysfunction: progressive orthopnea or orthopnea with paroxysmal nocturnal dyspnea. Often present at end of second trimester or in early postpartum period when fluid shifts occur | Echocardiogram | Diuretics, beta-blockers as indicated. ACE inhibitors contraindicated in pregnancy |
| Arrhythmia | Sudden onset and cessation, associated sensation of palpitations or chest discomfort | Electrocardiogram, Holter or event monitor | Beta-blockers, calcium channel blockers |
| Venous thromboembolism | Sudden onset, any trimester. May have associated DVT features | Computerized tomography pulmonary angiogram, V/Q scan, lower-extremity Dopplers | Anticoagulation with injectable heparins in pregnancy, warfarin in the postpartum period. |
Asthma in pregnancy
Asthma is the most common chronic medical illness to complicate pregnancy, affecting between 6% and 12% of all pregnancies . It is often undiagnosed and, even when recognized, may be undertreated. Pregnancy provides an opportunity to diagnose asthma and to optimize the treatment of women already known to have asthma.
The course of asthma is typically unpredictable in pregnancy, and studies have suggested that about one-third of patients improve, one-third remain the same, and a third worsen . Factors contributing to improvement may be the pregnancy-associated rise in serum cortisol and/or the increase in progesterone, which acts as a potent smooth muscle relaxant. Acute asthma in labor is unlikely because cortisol levels at term are around four times the prepregnancy levels . Women whose symptoms improve during the last trimester of pregnancy may experience a postpartum flare-up. Factors contributing to worsening include the increased incidence of gastroesophageal reflux disease (GERD) and gestational rhinitis, which leads to postnatal drip . Deterioration in disease control is commonly caused by a reduction or even complete cessation of medications due to patient fears about their safety, although this aspect has reduced significantly in recent years .
Case–control studies have shown that well-controlled pregnant asthmatic patients do not have a significantly higher rate of adverse outcomes than women without asthma . Women with documented frequent exacerbations are more likely to have miscarriages , and suboptimal control appears to be associated with low birth weight and intrauterine growth restriction. Chronic or intermittent maternal hypoxemia is usually offered as the explanation for the above, although it should be noted that the majority of women with even poorly controlled asthma are unlikely to have chronic hypoxia to the degree that would explain these obstetric outcomes.
The National Asthma Expert Panel Report classifies asthma severity into four categories: intermittent, mild persistent, moderate persistent, and severe persistent. Patients within each category can be classified as well controlled, not well controlled, or poorly controlled. This classification is very useful in directing appropriate management with step therapy. The first step in the management is establishing the diagnosis of asthma. The next step is the identification and avoidance of triggers. Identification and treatment of GERD, sinus disease, and allergic or gestational rhinitis will help control symptoms. Compliance and proper use of medications are paramount. Monitoring peak flows, reviewing inhaler techniques on a regular basis, and the provision and adherence to an asthma management plan have all been shown to reduce the frequency and severity of asthma exacerbations.
The National Asthma Education and Prevention Program (NAEPP) published guidelines on the pharmacological management of pregnant patients with asthma in 2004 after reviewing extensive data on the fetal safety of all the available drugs. Table 2 summarizes a stepwise approach to the management of asthma. Mild intermittent asthma should be managed with an inhaled short-acting “reliever” (beta-agonist) medication as required (step 1). If this usage exceeds once daily, regular inhaled anti-inflammatory medication with a steroid “preventer” inhaler should be commenced (step 2). The next step in therapy is either the addition of a long-acting reliever or an increase in the dose of inhaled steroid (step 3). Further steps involve a trial of additional therapies such as leukotriene receptor antagonist (step 4). If all of the above measures fail to achieve adequate control, then frequent or continuous use of oral steroids becomes necessary (step 5). It is vital that any woman who is still smoking be advised to cease immediately as this undoubtedly acts as a major trigger factor. All of the above medications have been shown to be safe in pregnancy and lactation. This should be emphasized in preconception or early pregnancy counseling, so that women do not self-cease important anti-inflammatory inhaled therapy. Pregnant women with asthma should be asked about a history of aspirin sensitivity before being advised to take low-dose aspirin (e.g., preeclampsia prophylaxis or antiphospholipid antibody syndrome). If the patient is identified as having GERD, treatment with a proton pump inhibitor or histamine H2 blocker should be instituted.
| Step 1 (mild intermittent) | No daily medication needed. Short-acting inhaled beta2-agonists (albuterol: ®Ventolin and ®Proair) as needed for symptoms |
| Step 2 (mild persistent) | Low-dose inhaled corticosteroids |
| Step 3 (moderate persistent, daily symptoms) | Low-dose inhaled corticosteroids plus long-acting beta2-agonist OR medium-dose inhaled corticosteroids |
| Step 4 (Severe persistent, continual symptoms, frequent nocturnal symptoms) | High-dose inhaled corticosteroids plus long-acting inhaled beta2-agonist and, if needed, systemic steroids |
In the management of an acute exacerbation, tachypnea and raised PaCO 2 level (above the normal pregnancy range) should prompt the suspicion of impending respiratory failure. The early use of noninvasive ventilation (NIV) and/or intubation should be considered in these cases .
With regard to fetal testing, a routine third-trimester ultrasound can be considered in a woman with well-controlled asthma with appropriate growth in the fundal height. The NAEPP Working Group recommends serial ultrasounds starting at 32 weeks of gestation in women with suboptimally controlled asthma and women with moderate to severe asthma . If the growth is not appropriate, fetal testing should be started. Testing may include non-stress testing (NST), biophysical profiles (BPP), and/or umbilical artery Doppler flow studies. The frequency of such testing would depend on the severity of the patient’s asthma or on the degree of growth restriction. It is advisable to administer stress dose steroids at the time of labor and delivery to patients who have been on prolonged systemic steroids during the pregnancy . Both prostaglandin E2 and oxytocin can be used as induction agents. The use of 15-methyl prostaglandin F2-alpha to treat life-threatening postpartum hemorrhage may be unavoidable, but it should be used with caution in women with asthma as it can cause bronchospasm. Fentanyl is preferred to morphine and meperidine, both of which can release histamine and result in bronchoconstriction. Epidural anesthesia is advised as it reduces oxygen consumption and minute ventilation, as well as reducing the possibility of requiring general anesthesia if an emergency cesarean section is indicated during labor.
During the postpartum period, women should be counseled to continue on the same asthma medications to reduce the likelihood of a flare-up. All of the drugs discussed above can be safely used during lactation. Breast-feeding should be encouraged as it appears to reduce the likelihood of the offspring developing asthma and other atopies , most likely due to the delay in introduction of cow’s milk.
Pneumonia in pregnancy
Pregnant patients are susceptible to the same respiratory diseases as the nonpregnant patient, and for the most part they should be treated similarly. Pneumonia is the most common cause of fatal non-obstetric infection in the pregnant patient . Peripartum risk factors such as delivery by cesarean section can increase the risk of hospital admission for pneumonia in the postpartum period . Pneumonia in pregnancy can also lead to an increased likelihood of a complicated delivery compared to pregnancies in which infection is absent .
Pregnant patients have several characteristics specific to pregnancy predisposing them to an increased incidence and risk of complications from pneumonia . These include immunologic changes such as altered T lymphocyte immunity; maternal physiologic changes such as increased oxygen consumption, increase in lung water, and elevation of the diaphragm; and the higher likelihood of aspiration during labor and delivery. Coexisting illness or habits may also increase the risk of pneumonia in the peripartum period such as smoking, underlying lung disease such as asthma, cystic fibrosis, HIV infection, or immunosuppressive therapy for other chronic conditions.
The etiologies of pneumonia in pregnancy are similar to those in the nonpregnant host, and often no etiologic agent is identified . Bacterial, viral (with the risk of secondary bacterial infection), fungal, and mycobacterial etiologies are all possible. Like the nonpregnant host, common bacterial pathogens in community-acquired pneumonia include Streptococcus pneumoniae , Haemophilus influenzae , as well as atypical bacterial pathogens such as Legionella species, Mycoplasma pneumoniae , and Chlamydophila pneumoniae . Staphylococcus aureus (including methicillin-resistant strains) is also a possible cause of pneumonia, and it can be associated with a secondary infection after an influenza illness. Health-care-associated organisms are less common and are usually present in those with other comorbidities, including cystic fibrosis . Pneumocystis jirovecii should be considered in a pregnant woman with human immunodeficiency syndrome (HIV), especially with a low CD4 cell count. Viral agents include influenza and rarely varicella. Up to 9% of primary cases of varicella during pregnancy can be complicated by pneumonia . Fungal etiologies such as coccidiomycosis are rare.
The clinical presentation in pregnant women with pneumonia is similar to that in nonpregnant women. Fever, cough, dyspnea, and hypoxia are part of the common presentation. Some experts advise that the inpatient and ICU admission criteria for pregnant woman should be liberalized, as there is a decreased ability to tolerate hypoxia in the pregnant patient . Potential indications for ICU admissions, according to the American Thoracic Society/Infectious Disease Society of America, include but are not limited to the need for mechanical ventilation, septic shock requiring vasopressors, respiratory rate of >30 breaths per minute, PaO 2 /FiO 2 ratio <250 mmHg, multilobar infiltrates, confusion or disorientation, platelets <100,000 per mm 3 , white blood cell count <400 per mm 3 , hypotension, and hypothermia . These criteria are not specific to pregnant patients, and the threshold for admission to the intensive care unit (ICU) in pregnancy should likely be lower than for the nonpregnant host. Influenza is a known risk factor to increase hospitalizations, ICU admissions, and death in the pregnant patient. As pregnant women appear to be more vulnerable to severe, life-threatening respiratory disease such as influenza, they should be managed aggressively with supportive care and prompt administration of antiviral medication (such as oseltamivir or zanamivir), ideally within 48 h of symptom onset .
The treatment for pneumonia in pregnancy is largely the same as in the nonpregnant patient, with some notable exceptions. Community-acquired pneumonia is often treated with a cephalosporin for typical bacterial pathogens such as S. pneumoniae and H. influenzae , as well as a macrolide such as azithromycin for atypical bacterial pathogens such as M. pneumoniae , Legionella pneumophila , or C. pneumoniae . Both of these classes of antibiotics can be used safely in pregnancy. The fluoroquinolones, which are often used to treat community-acquired pneumonia in the outpatient setting, are generally not used in pregnancy secondary to concerns of arthropathy in immature animals and potential fetal toxicity. Tetracyclines are also not used as they have been associated with the staining of fetal teeth and bony deformities. Although not routinely recommended, sputum cultures can be performed and the results can be used to tailor therapy according to the pathogen recovered.
Viral pneumonia in pregnancy deserves special mention in light of the recent influenza epidemics. Influenza in pregnancy is clearly associated with an increased rate of morbidity and mortality . One of the complications of influenza is pneumonia – either a secondary bacterial pneumonia or a primary viral pneumonia. Autopsy findings from the influenza outbreak of 1957 revealed that pregnant women who died were more likely to have a viral pneumonia, compared to nonpregnant women who were more likely to have a secondary bacterial pneumonia with pathogens such as S. aureus , pneumococcus, or H. influenzae . Either can lead to florid respiratory failure, and antibacterials, antivirals, and supportive care are required.
Varicella pneumonia is the most common complication of primary varicella infection in the nonimmune host, and although uncommon, it is much more common in pregnancy and in the adult, compared to primary infection in childhood. Primary varicella infection is also more severe in pregnancy with a mortality of 35–40% in the pregnant patient compared to a mortality of 11–17% outside of pregnancy . Treatment with acyclovir should be initiated and it may decrease mortality .
Acute respiratory distress syndrome in pregnancy
Acute respiratory distress syndrome (ARDS) is an acute, diffuse, inflammatory lung injury that leads to increased pulmonary vascular permeability, increased lung weight, and a loss of aerated tissue . The clinical hallmarks of ARDS are hypoxemia and bilateral radiographic opacities, while the pathological hallmark is diffuse alveolar damage (i.e., alveolar edema with or without focal hemorrhage, acute inflammation of the alveolar walls, and hyaline membranes).
The severity of the hypoxemia defines the severity of the ARDS. Table 3 describes the clinical features that define the illness.
